Description: The overall hypothesis of this PPA is to identify risk assessment of certain genetic markers such as miRNAs, single nucleotide mismatch repair genes or SNPs, and X-linked genes (such as TSPX) since there is evidence that they are associated with prostate cancer. The first project is to investigate the miRNAs that may serve as markers of prostate cancer by virtue of their action in suppression of oncogenic or tumor suppressor gene expression. The studies aim at delineating the underlying mechanisms that control these processes. The second project is to investigate the role of SNPs in mismatched repair (MMR) genes in prostate cancer susceptibility and progression. The third project is to investigate involvement in prostate cancer risk of the X-linked tumor suppressor gene (TSPX) which is a tumor repressor and corepressor for AR functions for its involvement in prostate cancer risk and progression. The three projects in the PPA will be supported by three Cores: 1) Administrative Core; 2) Tissue/Morphology/Molecular Core; and 3) Statistical Core. Significance: Strengths: The study of the expression of three types of molecular biomarkers of prostate cancer in a large number prostate specimens (at different stages of pathology) represents an important step towards developing a system of patient identification with respect to their potential for disease progression. This knowledge could be of much value in devising therapy approaches. This research will also contribute to the aspect of knowledge on prostate cancer pathobiology that is currently missing. Studies on the molecular mechanisms of the functions of the three types of biomarkers are also well considered and will advance the fundamental knowledge pertaining to the function of these biomarkers. A particularly noteworthy point is that investigation of molecular biomarkers along the proposed lines has not been undertaken previously making this a highly novel endeavor. The success in the proposed studies could lea